Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 34, Pages 38562-38574Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.2c11117
Keywords
ischemia; reperfusion injury; myocardial infarction; nanocarriers; silica cross-linked micelles; targeted delivery
Funding
- National Natural Science Foundation of China [81971725, 81702998, 81701766]
- Program of Distinguished Professor of Jiangsu Province (2020)
- Qing Lan Project of Jiangsu Province
- Six Talent Peaks Program of Jiangsu Province [SWYY-104]
- Singapore National Research Foundation Investigatorship [NRF-NRFI2018-03]
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Cardioprotective medication has limited effectiveness in relieving myocardial ischemia/reperfusion (I/R) injury. By using nanomedicine for myocardium-targeted delivery, the concentration of therapeutic drugs in the injured myocardium can be significantly increased, leading to effective protection against cardiac damage.
Cardioprotective medication is the common treatment to relieve myocardial ischemia/reperfusion (I/R) injury. However, limited by the low bioavailability of therapeutic drugs, the therapeutic outcome is barely satisfactory. Because the I/R injury can enhance the permeability of the vasculature and allow the extravasation of nanoparticles into the surrounding tissue, herein we formulate the cardiotonic drug olprinone (Olp) in cross-linked micelles as the nanomedicine to achieve myocardium-targeted delivery after systematic administration. As a result, the local concentration of Olp in the injured myocardium is raised by orders of magnitude with prolonged drug duration time. The treatment successfully preserves the pumping efficiency of the heart, alleviates ventricular remodeling, and thus stops the positive feedback loop for the deteriorated cardiac function. Consequently, the myocardium-targeted nanomedicine significantly salvages the heart from I/R injury before irreversible pathological changes take place.
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